GM1 IgM Autoantibodies

GM1 is expressed in the peripheral nervous system in the nodes of Ranvier, outer myelin, and the end plates of motor neurons.⁹ Measurement of IgM antibodies to GM1 (Anti-GM1) has been employed in the evaluation of with chronic neuropathies that affect the motor nerves. IgM Anti-GM1 seropositivity is significantly associated with multifocal motor neuropathy (MMN).^5,7,9-11 MMN is a purely motor neuropathy (without sensory loss) that is characterized by progressive, asymmetric muscle weakness and atrophy of limbs.^11-17 The hallmark of MMN is the presence of conduction block CB with normal sensory nerve conduction across the region of block.¹³ The reported prevalence of IgM Anti-GM1 positivity in MMN varies widely (25% to 85%) in the literature, depending on the clinical definition and detection techniques used in various studies.^9,12,18-20 Testing for Anti-GM1 was included among the possible supportive laboratory test for the diagnosis of MMN by the Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society.²¹ Higher titers of Anti-GM1 are associated with greater clinical severity in MMN patients but are rare in most other neurological disorders such as ALS and chronic inflammatory demyelinating polyneuropathy.^2,20

The underlying cause of MMN is poorly understood but clinical studies suggest that Anti-GM1 autoantibodies directed against myelin antigens, along with autoreactive T cells and macrophages that invade myelin sheath play a causative role.^16,22-23 Anti-GM1 antibodies have been shown to bind to the surface of motor neurons, the nodes of Ranvier, and at the neuromuscular junction, where they may exert their effects.⁹ An autoimmune etiology is further supported the fact that immune modulating therapy improves symptoms for most patients.^12,16,22 Approximately 80% of patients with MMN respond to intravenous mmunoglobulins (IVIg). It is important to distinguish MMN from other motor neuron diseases with similar symptoms that are unresponsive to this treatment.^13-15 The clinical presentation of MMN can closely mimic several neurological conditions including those with more malignant prognoses such as motor neuron disease.²⁴ There is further value in distinguishing MMN from other immune mediated neuropathies that are responsive to plasma exchanges and steroids, as correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.^15,25-27Testing for anti-GM1 can be useful in cases where MMN is clinically suspected but conduction block is not evident or is in less accessible nerve segments.³